Mboni-Johnston, I.M.; Kouidrat, N.M.Z.; Hirsch, C.; Weber, A.G.; Meißner, A.; Adjaye, J.; Schupp, N. Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins. Int. J. Mol. Sci.2024, 25, 81.
Mboni-Johnston, I.M.; Kouidrat, N.M.Z.; Hirsch, C.; Weber, A.G.; Meißner, A.; Adjaye, J.; Schupp, N. Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins. Int. J. Mol. Sci. 2024, 25, 81.
Mboni-Johnston, I.M.; Kouidrat, N.M.Z.; Hirsch, C.; Weber, A.G.; Meißner, A.; Adjaye, J.; Schupp, N. Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins. Int. J. Mol. Sci.2024, 25, 81.
Mboni-Johnston, I.M.; Kouidrat, N.M.Z.; Hirsch, C.; Weber, A.G.; Meißner, A.; Adjaye, J.; Schupp, N. Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins. Int. J. Mol. Sci. 2024, 25, 81.
Abstract
Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the regain of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it would be beneficial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, exhibiting a similar morphology to PTEC, expressing prototypical PTEC markers and performing albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.
Keywords
hiPSC; differentiation; regeneration; cisplatin; cyclosporin A
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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